Platelet-derived growth factor B-chain gene expression in mesangial cells: Effect of phorbol ester on gene transcription and mRNA stability

1994 ◽  
Vol 140 (1) ◽  
pp. 31-36 ◽  
Author(s):  
Basant Bhandari ◽  
Kathleen Woodruff ◽  
Hanna E. Abboud
1992 ◽  
Vol 262 (2) ◽  
pp. L140-L146 ◽  
Author(s):  
R. N. Han ◽  
S. Buch ◽  
B. A. Freeman ◽  
M. Post ◽  
A. K. Tanswell

The expression of platelet-derived growth factor (PDGF), its receptor, and related genes was studied in the lung tissue of rats exposed to air or 85% O2. PDGF-B chain mRNA was increased by 6 days and PDGF B-type receptor mRNA was increased by 4 and 6 days of exposure to 85% O2. Despite a continued increase of cell division, both PDGF-B chain and B-type receptor mRNAs had returned to control values by 14 days of exposure to 85% O2. PDGF-A chain mRNA was unaffected by exposure to 85% O2. Nuclear runoff transcription analysis confirmed increased transcription of PDGF-B chain mRNA, whereas Western blot analysis of lung homogenates suggested consequent increased translation of PDGF-B chain mRNA to PDGF-BB at 7 days of exposure to 85% O2. Combined immunocytochemistry and autoradiography localized PDGF-BB to the major site of cell division, the pulmonary interstitium. We speculate that the early pulmonary fibroblast hyperplasia observed following exposure to 85% O2 is mediated by increased PDGF-B chain gene expression and may also be mediated by changes in PDGF B-type receptor gene expression.


1995 ◽  
Vol 307 (1) ◽  
pp. 159-167 ◽  
Author(s):  
J K Heath ◽  
J Southby ◽  
S Fukumoto ◽  
L M O'Keeffe ◽  
T J Martin ◽  
...  

Epidermal growth factor (EGF) produced rapid and striking effects on parathyroid hormone-related protein (PTHrP) gene expression in the immortalized human keratinocyte cell line, HaCaT. Steady-state levels of PTHrP mRNA and secreted PTHrP were increased 10-fold by maximally effective concentrations of EGF. EGF increased both PTHrP gene transcription and PTHrP mRNA stability. Nuclear run-on assays demonstrated a 4-fold increase in transcriptional rate in EGF-stimulated cells while transient transfection analysis indicated that the action of EGF on transcription involved both the GC-rich promoter, P2, and the downstream TATA promoter, P3, but apparently not the upstream TATA promoter, P1. In experiments where EGF treatment produced more stable PTHrP transcripts, the half-life of c-fos mRNA was unaltered, suggesting a relatively specific effect of EGF. Moreover, only those species of PTHrP mRNA containing two of the alternative 3′ exons (exons VII and VIII) were stable, those containing exon IX were not. Reverse-transcription PCR demonstrated that EGF produced differential increases in the abundance of PTHrP mRNA species initiated by the three PTHrP promoters. The major effect was seen on the abundance of transcripts initiated by P1 and P2, with less marked regulation of P3-initiated transcripts. Thus EGF regulation of PTHrP gene expression in HaCaT cells is multifactorial and the combination of its actions at the 5′ and 3′ ends of the gene favours the accumulation of subpopulations of PTHrP mRNA containing exons I, VII and VIII.


Sign in / Sign up

Export Citation Format

Share Document